Mayo Clin Proc, December 2002, Vol 77 Heart Rate Response After Cardiac Transplantation 1295 Mayo Clin Proc. 2002;77:1295-1300 1295 © 2002 Mayo Foundation for Medical Education and Research Original Article Partial Normalization of the Heart Rate Response to Exercise After Cardiac Transplantation: Frequency and Relationship to Exercise Capacity RAY W. SQUIRES, PHD; TAT-CHI LEUNG, MBCHB, MRCP; NANCY S. CYR, BS; THOMAS G. ALLISON, PHD; BRUCE D. JOHNSON, PHD; KARLA V. BALLMAN, PHD; JEAN A. WAGNER, RN CNP; LYLE J. OLSON, MD; ROBERT P. FRANTZ, MD; BROOKS S. EDWARDS, MD; SUDHIR S. KUSHWAHA, MD; JOSEPH A. DEARANI, MD; RICHARD C. DALY, MD; CHRISTOPHER G. A. MCGREGOR, MD; AND RICHARD J. RODEHEFFER, MD From the Division of Cardiovascular Diseases and Internal Medicine (R.W.S., T.-C.L., N.S.C., T.G.A., B.D.J., J.A.W., L.J.O., R.P.F., B.S.E., S.S.K., R.J.R.), Division of Biostatistics (K.V.B.), and Division of Transplantation Surgery (J.A.D., R.C.D., C.G.A.M.), Mayo Clinic, Rochester, Minn. Dr Leung is now with the Pamela Youde Nether- sole Eastern Hospital, Chai Wan, Hong Kong. Address reprint requests and correspondence to Ray W. Squires, PhD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: squires.ray@mayo.edu). • Objective: To determine the frequency of partial nor- malization of the heart rate response to graded exercise and its relationship to exercise capacity in cardiac trans- plant recipients. • Subjects and Methods: The study subjects were 95 adults (77 men, 18 women) who were available to perform a cardiopulmonary exercise test 1 year after orthotopic cardiac transplantation, which occurred between June 1988 and September 1998. All subjects received standard immunosuppressant medications. At the time of the exer- cise tests, the mean ± SD age of the subjects was 49±14 years. The mean ± SD resting left ventricular ejection fraction was 62%±8%. All subjects participated in a 6- to 8-week supervised exercise program, starting no later than 1 month after surgery. Subjects were given an exercise prescription for independent exercise training after finish- ing the supervised program. Self-reported weekly exercise training had a median value of 90 minutes (interquartile range, 0-210 minutes). Symptom-limited graded exercise was performed on a treadmill, with breath-by-breath analysis of expired air. • Results: For the entire cohort, peak exercise oxygen uptake was 19.9±4.8 mL · kg –1 · min –1 (61%± 15% of age V · O 2 = oxygen uptake; V · O 2 peak = peak exercise oxygen uptake and sex predicted). Thirty-two subjects (34%) had a par- tially normalized heart rate response to graded exer- cise. The frequency was similar for men (25/77 [33%]) and for women (7/18 [39%]) and was independent of recip- ient or donor age. Peak exercise heart rate (147±18 vs 134±21 beats/min; P=.008) and heart rate reserve (46±15 vs 33±15 beats/min; P<.001) were greater for subjects with a partial normalization of heart rate response. Peak exercise oxygen uptake was similar for subjects with or without partial normalization of the heart rate response (20.9±5.8 vs 19.4±4.2 mL · kg –1 · min –1 ; P=.22). Submaximal exercise oxygen uptake during the first few minutes of ex- ercise was also not affected by normalization of the heart rate response. • Conclusion: At 1 year after cardiac transplantation, approximately one third of subjects had partial normaliza- tion of the heart rate response to graded exercise. However, a higher peak exercise heart rate and a larger heart rate reserve did not result in better aerobic exercise capacity. Mayo Clin Proc. 2002;77:1295-1300 C ardiac transplantation results in complete denervation of the myocardium. 1 The loss of autonomic nervous system innervation results in an abnormal heart rate response to graded exercise testing that is related in part to dependence on the levels of circulating catecholamines for heart rate control. 2 As shown in Figure 1, the resting heart rate is elevated, there is only a minimal increase in rate during the first few minutes of exercise, the maximal heart rate occurs in the recovery period after exercise rather than at peak exercise, and there is a plateau in heart rate during recovery from exercise with a slow return to resting values. In cardiac transplant recipients, the chronotropic reserve is reduced, and exercise capacity is usually below normal compared with subjects who have undergone coronary artery bypass surgery. 4 The below-normal exercise capacity may 5 or may not 6 be related to the reduced chronotropic responsiveness. Until recently, denervation was thought to be perma- nent. However, several investigators, using diverse meth- ods such as uptake of the norepinephrine analogue C-11 hydroxyephedrine measured by positron emission tomog- raphy, 5 heart rate responsiveness to intracoronary tyramine infusion, 6 and uptake of iobenguane by myocardial sympa- thetic fibers, 7 showed sympathetic nervous system reinner- vation in some cardiac transplant recipients months to years after surgery. Several investigators have reported an increase in heart rate in most subjects during maximal exercise during the For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.